Bone fractures more common in anticonvulsant users
Anticonvulsant users are at increased risk of fracture and should undergo regular bone health monitoring, according to Australian researchers.
A study of 1458 patients with radiologically-confirmed bone fractures and 1796 controls showed anticonvulsant use was associated with a 2.8- and 1.8-fold higher fracture risk in men and women, respectively, regardless of demographic, lifestyle, medical and medication-related factors, the authors wrote in the Journal of Musculoskeletal and Neuronal Interactions.
Although further research on underlying mechanisms is needed, previous studies have suggested cytochrome P450-inducing drugs topiramate, phenytoin and phenobarbiturate could increase fracture risk by upregulating enzymes involved in vitamin D metabolism.
“These enzymes convert 25-hydroxy vitamin D (25(OH)D) into inactive metabolites that lead to calcium resorption with consecutive secondary hyperparathyroidism,” they wrote.
“This unavailability of vitamin D is thought to lead to reduced bone mineralisation, which, when coupled with compensatory increases in parathyroid hormone (PTH) production, could lead to increased bone resorption and a net low bone turnover state.”
Non-enzyme-inducing agents have also contributed to bone loss, with pre-clinical studies showing valproic acid significantly decreased osteonectin and collagen I concentration in osteoblast-like cell lines, impacted cytoskeleton arrangement in osteoblast and fibroblast cell lines and altered microtubule cytoskeleton and actin filaments in mouse embryos, where it was implicated in teratogenic skeletal phenotypes.
“Potential mechanisms are yet to be explored; however, this work supports others in suggesting a cautious approach and regular monitoring of bone health in those prescribed anticonvulsants,” the authors concluded.
Warning on hypertension with erenumab
The Product Information (PI) for the CGRP inhibitor erenumab (Aimovig) has been updated with a warning statement about a potential causal relationship between the drug and hypertension.
It follows an analysis of 61 postmarketing case reports of elevated BP occurring most frequently (46%) within a week of the first dose of erenumab.
The median change in blood pressure was 43 mm Hg systolic and 29 mm Hg diastolic for the 70 mg dose of erenumab and 40 mmHg / 24 mm Hg for the 140 mg dose.
Forty-one cases were classified as serious, including seven that resulted in hospitalisation and and four identified as incurring disability. Many required pharmacological intervention.
The investigators said the temporal relationship supported an association between elevated BP and use of erenumab.
There has been one report of hypertension associated with erenumab reported in Australia to the TGA.
Healthcare worker vaccination reduces COVID-19 transmission
In findings described reassuring for healthcare workers and their families, a UK study has provided evidence suggesting that COVID-19 vaccination of healthcare staff reduces transmission within their household.
Researchers in the UK evaluated data from almost 200,000 household members of 144,525 health care workers in Scotland who worked from March to November 2020.
At the time of the study, 78% of healthcare workers had received at least one dose of either Pfizer or the AstraZeneca vaccine, and 25% had received a second dose.
The analysis found that risk of COVID-19 among household members of vaccinated health care workers was 30% lower (Hazard Ratio 0.70) after the first dose and more than 50% lower (HR 0.46) after the second dose of vaccine.
The effect of vaccination may have been larger because the analysis did not cover risk of transmission from sources outside the household, the researchers wrote in NEJM.
“Given that vaccination reduces asymptomatic infection with SARS-CoV-2, it is plausible that vaccination reduces transmission,” said the researchers, led by Dr Anoop Shah of the London School of Hygiene and Tropical Medicine.